Molecular mechanisms underlying the anti-Colon Cancer effects of Caulerpa lentillifera polysaccharides (CLP)

Colon cancer (CC) ranks is the second leading cause of cancer-related deaths globally. Despite chemotherapy being a primary treatment its effectiveness significantly declines in advanced in stage. Emerging evidence suggests that dietary components particularly polysaccharides, play a role in CC progression. This study employed multi-omics and network pharmacology to elucidate the mechanisms underlying the apoptotic effects of Caulerpa lentillifera polysaccharide (CLP) in CC, validated through in vitro and in vivo experiments. Transcriptomics and network pharmacology analysis identified the p53/Bax/Caspase-3 pathway as a key regulatory axis. Further targeted analysis of amino acid metabolism revealed that CLP significantly decreased intracellular aspartate (Asp) levels. Additionally, reactive oxygen species (ROS) accumulation was detected in cells. CLP treatment reduced Asp content, leading to ROS accumulation, which activated the p53/Bax/Caspase-3 pathway, triggering apoptosis. In vivo, CLP effectively inhibited tumor growth in BALB/c mice bearing CT26 colon cancer cells. These findings suggest that CLP exerts anti-colon cancer effects by modulating amino acid metabolism and inducing apoptosis via the p53/Bax/Caspase-3 axis, providing a promising therapeutic strategy for CC.